Darolutamide 300mg tablets

Background and objectiveMetastatic hormone-sensitive prostate cancer (mHSPC) patients with visceral disease (VD) represent a high-risk subgroup associated with poor prognosis. Despite the introduction of treatment intensification strategies, the optimal systemic therapy for these patients remains unclear. This network meta-analysis (NMA) aims to evaluate the efficacy of the current therapeutic combinations in terms of overall survival (OS) in the subgroup of patients with VD.MethodsA systematic review and NMA was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines (PROSPERO: CRD42025642120). Phase 3 randomised controlled trials assessing systemic therapies for mHSPC were identified through the PubMed, Cochrane, and Embase databases. Only studies reporting OS outcomes for patients with VD were included. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and analysed using a frequentist NMA framework. The risk of bias was assessed using the Confidence in Network Meta-Analysis (CINeMA) tool.Key findings and limitationsEight phase 3 trials (7944 patients, 1189 with VD) were included. The androgen deprivation therapy (ADT) + docetaxel + darolutamide combination was the most effective regimen (HR = 0.42, 95% CI: 0.21-0.82). Among doublets, ADT + docetaxel (HR = 0.53, 95% CI: 0.30-0.93) and ADT + abiraterone (HR = 0.58, 95% CI: 0.41-0.83) showed superior efficacy to other androgen receptor pathway inhibitor-based doublet regimens, including combinations with enzalutamide, apalutamide, and darolutamide. The absence of individual patient data and the lack of efficacy data stratified by metastatic site (liver or lung involvement) were the key limitations.Conclusions and clinical implicationsTreatment intensification with triplet therapy (ADT + docetaxel + darolutamide) provides the greatest OS benefit in mHSPC patients with VD. Doublet regimens incorporating chemotherapy or abiraterone remain viable alternatives. Further prospective studies are needed to refine treatment selection based on VD-specific biology and organ-specific metastatic patterns.

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Aim: Recent network meta-analyses (NMAs) in metastatic castration-sensitive prostate cancer have not adequately addressed potential treatment effect modifiers and population imbalances, which introduces bias. Although, individual-patient data (IPD) are seldom available across all trials, recent methodological advances allow adjustments using a combination of IPD and aggregate data. Materials & methods: IPD from the ARASENS trial (darolutamide + docetaxel + androgen-deprivation-therapy [ADT]) and aggregate data from a systematic review were analyzed. Two methods were used to adjust for population imbalances: multilevel network meta-regression (ML-NMR) using baseline characteristics, and network meta-interpolation (NMI) using subgroup data. Relative effects were estimated for an ARASENS-like population, with sensitivity analysis in an average trial population. Results: Twelve studies, including ARASENS, were included. All studies reported baseline characteristics for ML-NMR. Sufficient subgroup data for NMI were available in 8/12 studies for overall survival (OS) and 5/12 studies for progression-free survival (PFS). Darolutamide + docetaxel + ADT showed significant benefit over docetaxel + ADT, ADT and standard-nonsteroidal-antiandrogen + ADT in all analyses. ML-NMR showed improved OS for darolutamide + docetaxel + ADT compared with abiraterone + docetaxel + ADT, apalutamide + ADT, enzalutamide + ADT and abiraterone + ADT. ML-NMR also showed improved PFS for darolutamide + docetaxel + ADT compared with apalutamide + ADT and enzalutamide + ADT. Using NMI, darolutamide + docetaxel + ADT demonstrated OS benefit over abiraterone + ADT and PFS benefit relative to abiraterone + ADT and apalutamide + ADT. Findings were consistent in an average population, although ML-NMR did not show significant OS benefit of darolutamide + docetaxel + ADT over apalutamide+ADT. Conclusion: Improved outcomes were observedwith darolutamide+docetaxel+ADT compared with other therapies. By incorporating effect modifiers and addressing population imbalances, we provide clinicians with a more accurate understanding of treatment efficacy for better-informed decision-making.

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BackgroundDarolutamide is the next-generation androgen receptor inhibitor approved for the treatment of advanced prostate cancer, including non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic hormone-sensitive prostate cancer (mHSPC). However, the efficacy and safety of darolutamide are nonetheless worthy of further clinical studies. The objective of this meta-analysis was to evaluate the overall survival, metastasis-free survival and various specific adverse events of darolutamide combination therapy in patients with mHSPC or nmCRPC.MethodsThis meta-analysis was performed on PubMed, EMBASE, Web of Science, ClinicalTrials.gov, and the Cochrane Library for English-language articles to collect randomized clinical trials of darolutamide combination therapy in mHSPC and nmCRPC from the start of the database to 15 January 2026. The primary efficacy outcomes were overall survival and metastasis-free survival. Key safety outcomes included the total number of overall adverse events, the total number of grade ≥3 adverse events and serious adverse events, and the occurrence of specific adverse events of interest. The risk of bias was assessed by the Cochrane risk-of-bias tool for randomized trials (RoB 2). Publication bias was assessed by funnel plots.ResultsThere were 8 research articles from 3 randomized clinical trials with 3,483 patients involved in this meta-analysis, including 1,509 nmCRPC patients from the ARAMIS trial, 1974 mHSPC patients from the ARASENS and ARANOTE trials. Combining darolutamide with ADT significantly prolonged overall survival (OS) and metastasis-free survival (MFS) in nmCRPC patients compared with placebo plus ADT. And darolutamide plus ADT with or without docetaxel also showed favorable overall survival in mHSPC patients. Subgroup meta-analyses of OS among mHSPC patients for baseline total PSA (tPSA) values and Gleason scores showed the beneficial efficacy of darolutamide in mHSPC. The addition of darolutamide in ADT and/or docetaxel did not lead to serious adverse events, like heart failure, bone fracture and hypertension, in both nmCRPC and mHSPC patients.ConclusionDarolutamide combination therapy was beneficial to the prognosis and demonstrated a favorable safety profile in patients with advanced prostate cancer.Systematic review registrationIdentifier CRD420251145736.

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ObjectiveAndrogen receptor pathway inhibitors (ARPIs) are cornerstone treatments for advanced prostate cancer; however, their potential to increase fall risk remains a significant clinical concern. This meta-analysis aims to provide a rigorous, drug-specific evaluation of the association between novel ARPIs and the risk of falls.MethodsWe systematically searched PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov for Phase 2 or 3 randomized controlled trials (RCTs) comparing ARPIs (enzalutamide, apalutamide, and darolutamide) with control groups (placebo or non-steroidal antiandrogens [NSAA]). The primary outcomes were risk ratios (RRs) for all-grade and grade ≥ 3 falls. To account for multiplicity across correlated outcomes and the limited number of studies, pooled RRs were estimated using random-effects models with the restricted maximum-likelihood (REML) method. All analyses were performed on a logarithmically transformed scale, with 97.5% confidence intervals (CIs). Prediction intervals (PIs) were calculated to assess the dispersion of effects. Subgroup analyses were stratified by specific ARPI agents, control types, and clinical stages.ResultsEleven RCTs involving 12,239 patients were included. Overall, ARPIs were significantly associated with the increased risk of all-grade falls (RR 2.00, 97.5% CI 1.46-2.73, P 2 = 77.6%; PI 0.67-5.99) and grade ≥ 3 falls (RR 2.15, 97.5% CI 1.32-3.52, P = 0.0008, I2 = 0%; PI 1.15-4.02). However, risk profiles varied substantially across individual agents. Enzalutamide was associated with the highest risk increase (RR 2.55 vs. placebo, 97.5% CI 1.62-4.01, I2 = 79.2%; RR 2.47 vs. NSAA, 97.5% CI 1.14-5.37, I2 = 71.8%), followed by apalutamide (RR 1.65, 97.5% CI 0.77-3.52, I2 = 87.2%). In contrast, darolutamide demonstrated a favorable safety profile with no statistically significant increase in the risk of all-grade falls (RR 1.25, 97.5% CI 0.87-1.79, I2 = 0%) or severe falls (RR 1.31, 97.5% CI 0.34-5.00).ConclusionsCurrent evidence indicates that the increased risk of falls associated with ARPI therapy varies significantly among individual agents, rather than being a uniform class effect. While enzalutamide and apalutamide are statistically associated with elevated fall risk, darolutamide appears to maintain a more favorable safety profile. However, these drug-specific comparisons remain exploratory due to subgroup imbalances. Clinicians should consider proactive fall-risk assessments and individualized treatment selection, particularly for elderly or frail populations.

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ObjectiveAndrogen receptor pathway inhibitors (ARPIs) have revolutionized prostate cancer treatment, but their cardiovascular safety profile requires comprehensive evaluation. This meta-analysis aims to examine the association between ARPI use and hypertension risk in prostate cancer patients.MethodsWe systematically searched PubMed, Web of Science, and ClinicalTrials.gov for randomized controlled trials comparing ARPIs with control. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models for all-grade and grade ≥ 3 hypertension. Subgroup analyses were performed by individual ARPI agents and combination therapies.ResultsTwenty-two studies (derived from 21 distinct randomized controlled trials) involving 22,420 patients were included for analysis. ARPIs significantly increased the risk of all-grade hypertension (RR 1.82, 95% CI 1.51-2.21, p ConclusionARPI treatment significantly increases hypertension risk in prostate cancer patients, with substantial variability among specific agents and regimens. Combination therapy poses the highest risk, while darolutamide demonstrated a lower risk profile in this indirect comparison. These findings support routine blood pressure monitoring and aggressive management in patients receiving ARPI therapy, particularly those with pre-existing cardiovascular risk factors.

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